U.S. patent application number 11/291667 was filed with the patent office on 2007-06-07 for method of selecting benefit agents/oils suitable for reducing surfactant damage.
This patent application is currently assigned to CONOPCO, Inc. d/b/a UNILEVER, CONOPCO, Inc. d/b/a UNILEVER. Invention is credited to Kavssery Parameswaran Ananthapadmanabhan, Alexander Lips, Martin Vethamuthu, Carol Vincent, Lin Yang.
Application Number | 20070129271 11/291667 |
Document ID | / |
Family ID | 38110566 |
Filed Date | 2007-06-07 |
United States Patent
Application |
20070129271 |
Kind Code |
A1 |
Yang; Lin ; et al. |
June 7, 2007 |
Method of selecting benefit agents/oils suitable for reducing
surfactant damage
Abstract
The invention provides a method selecting benefit agent(s)
suitable for reducing surfactant damage in compositions comprising
at least one surfactant and at least one benefit agent. The
reduction in damage is measurable by decrease in number of protein
binding sites in presence versus absence of benefit agent, or when
benefit agent has solubility outside a defined range.
Inventors: |
Yang; Lin; (Woodbridge,
CT) ; Vethamuthu; Martin; (Southbury, CT) ;
Vincent; Carol; (Trumbull, CT) ; Lips; Alexander;
(New Canaan, CT) ; Ananthapadmanabhan; Kavssery
Parameswaran; (Woodbury, CT) |
Correspondence
Address: |
UNILEVER INTELLECTUAL PROPERTY GROUP
700 SYLVAN AVENUE,
BLDG C2 SOUTH
ENGLEWOOD CLIFFS
NJ
07632-3100
US
|
Assignee: |
CONOPCO, Inc. d/b/a
UNILEVER
|
Family ID: |
38110566 |
Appl. No.: |
11/291667 |
Filed: |
December 1, 2005 |
Current U.S.
Class: |
510/130 |
Current CPC
Class: |
A61K 8/55 20130101; A61Q
19/10 20130101; A61K 8/442 20130101; A61K 2800/75 20130101; A61K
8/466 20130101; A61K 8/92 20130101; A61K 8/463 20130101; A61K 8/375
20130101 |
Class at
Publication: |
510/130 |
International
Class: |
A61K 8/00 20060101
A61K008/00 |
Claims
1. A method of selecting benefit agent or agents suitable to reduce
surfactant damage in compositions comprising at least one
surfactant and at least one benefit agent, wherein said reduction
is measurable by decrease in number of protein binding sites binded
by surfactant when benefit agent is present compared to when
benefit agent is absent, or compared to when benefit agent used has
solubility outside defined range, wherein said method comprises:
(1) determining the Hansen solubility parameter of said benefit
agent; and (2) selecting or using said benefit agent or agents
having a Hansen benefit agent solubility of 16.5 to 37.
2. A method according to claim 1, wherein said at least one
surfactant is anionic surfactant.
3. A method according to claim 1, wherein benefit agent oil or
agents has solubility Hansen of 17 to 30.
4. A method according to claim 1, wherein Hansen solubility
parameter of benefit agent is determined using molecular modeling
software.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a method of significantly
reducing surfactant damage (e.g., to skin or other
protein-containing substrate) by utilizing compositions comprising
benefit agents (e.g., oils, solvents) within a defined high
polarity window (wherein polarity is measured using "Hansen
Solubility Parameter" of the benefit agent). The invention further
relates to compositions, particularly compositions effective in
reducing skin/protein damage, comprising benefit agents/oils
falling within the defined polarity window. In another embodiment,
the invention relates to a method of selecting benefit agent/oils
or a class of benefit agents/oils which are best suited for
reducing surfactant damage in surfactant containing compositions
using knowledge of Hansen solubility.
BRIEF SUMMARY OF THE INVENTION
[0002] It is well known that surfactant/cleanser can be harsh and
damaging to the skin. Generally, it is believed this occurs at
least in part, because surfactant binds to proteins found in the
skin and thereby interferes with the role of the protein (e.g., in
maintaining healthy skin).
[0003] It is also well known to utilize personal care compositions
comprising benefit agents, such as oils. Oils are thought to
provide an occlusion barrier and to help alleviate skin dryness by,
for example, reducing water loss from the skin barrier.
[0004] Unexpectedly, applicants have now found that use of benefit
agent in surfactant containing personal care compositions (e.g.,
personal care liquids, bars, etc.), particularly benefit agent
falling within specific polarity parameters (i.e., the polarity of
the benefit agent or combination of benefit agents), leads to
reduced damage of skin/substrate normally caused by the surfactant
in such compositions. While not wishing to be bound by theory, it
is believed that benefit agents falling within the defined polarity
profiles act to inhibit the process of protein denaturing by
interacting with the protein, thereby effectively blocking the
binding site on the protein molecule that is available for
surfactant binding. It is this binding of surfactant to protein
which is believed largely responsible for the harmful impact of
surfactant on skin.
[0005] In one embodiment, the invention further relates to a method
of selecting benefit agents/oils suitable for reducing surfactant
damage using knowledge of Hansen solubility parameters.
[0006] The following references are noted: U.S. Pat. No. 6,699,824
to Dawson et al.; EP 1 051 468 (assigned to Unilever); U.S. Pat.
No. 6,380,150 to Toussaint et al.; JP 2004/203848 (assigned to Lion
Corp); EP 0 912 666 (assigned to Colgate); and WO 96/37594
(assigned to P&G).
[0007] None of the noted references teaches or suggests a method of
reducing surfactant damage to skin or other substrate using benefit
agents (e.g., oils, solvents) oils having a defined polarity, or a
method of selecting benefit agents or a class of benefit agents
suitable for reducing such damage.
BRIEF DESCRIPTION OF THE INVENTION
[0008] In one embodiment, the present invention relates to a method
of reducing surfactant damage (e.g., reducing surfactant binding to
skin proteins) which comprises using surfactant-containing
compositions (preferably, but not necessarily, liquid compositions)
comprising benefit agent or combination of benefit agents having
high polarity (within a defined polarity window). The polarity of a
benefit agent can in turn be expressed as a function of the Hansen
solubility parameter of the benefit agent.
[0009] In a preferred embodiment of the first embodiment, the
invention relates to a method of reducing surfactant damage in a
composition comprising surfactant or surfactants, preferably
comprising at least one anionic surfactant (generally anionic
surfactants are harsher than other surfactants on skin), wherein
said method comprises using, in addition to the surfactant or
surfactants, a benefit agent(s) with Hansen solubility parameter
between about 16.5 and 37 (see examples), preferably 17 and 30,
more preferably between 19 and 27.
[0010] In a second embodiment of the invention, the invention
comprises a method of selecting benefit agent to be used to reduce
surfactant damage in a composition comprising at least one
surfactant and benefit agent, wherein said process comprises (1)
determining Hansen solubility parameters (HSP) of the benefit agent
(e.g., by calculating the HSP using molecular modeling software,
such as ChemSW (Version 333), which uses an empirical group
contribution model to calculate HSP based on known chemical
structure); and (2) selecting said benefit agent(s) having HSP of
between 16.5 and 37 alone or in combination, preferably having HSP
of between 17 and 30, more preferably 19 and 27.
[0011] In a third embodiment, the invention relates to compositions
comprising surfactant and a benefit agent or combination of benefit
agents having HSP from 16.5 to 37. Such composition has reduced
surfactant damage (e.g., at least 5% fewer binding sites) relative
to compositions with same type and amount of surfactant(s)
comprising benefit agent(s) having HSP below 16.5 or above 37, or
relative to compositions with no benefit agent.
[0012] These and other aspects, features and advantages will become
apparent to those of ordinary skill in the art from a reading of
the following detailed description and the appended claims. For the
avoidance of doubt, any feature of one aspect of the present
invention may be utilized in any other aspect of the invention. It
is noted that the examples given in the description below are
intended to clarify the invention and are not intended to limit the
invention to those examples per se. Other than in the experimental
examples, or where otherwise indicated, all numbers expressing
quantities of ingredients or reaction conditions used herein are to
be understood as modified in all instances by the term "about".
Similarly, all percentages are weight/weight percentages of the
total composition unless otherwise indicated. Numerical ranges
expressed in the format "from x to y" are understood to include x
and y. When for a specific feature multiple preferred ranges are
described in the format "from x to y", it is understood that all
ranges combining the different endpoints are also contemplated.
Where the term "comprising" is used in the specification or claims,
it is not intended to exclude any terms, steps or features not
specifically recited. All temperatures are in degrees Celsius
(.degree. C.) unless specified otherwise. All measurements are in
Si units unless specified otherwise. All documents cited are--in
relevant part--incorporated herein by reference.
BRIEF DESCRIPTION OF THE FIGURES
[0013] FIG. 1 is a graph of surfactant deposition (i.e., deposition
of anionic surfactant sodium dodecyl sulfate, or SDS), measured in
micrograms/cm.sup.2 (analyzed by HPLC method) when measured alone
and when measured with various benefit agents (oils, solvents,
etc.). As noted, when measured in combination with triolein, a high
polarity oil having an HSP within the range defined by the
invention (HSP of 23.77) deposition decreases. This is a signal of
less surfactant binding. By contrast, when measured in combination
with dodecane (relatively non-polar oil of HSP 16.02), deposition
was about the same or higher (more binding).
[0014] FIG. 2 is a measure of the b* value (defined in protocol).
The figure shows that combination of SDS plus triolein (versus SDS
plus dodecane or SDS alone) have smaller b* value, which again is
indicative of less surfactant binding (associated with less
damage).
[0015] FIG. 3 shows that, as more oil is used, the oil induces
aggregation of protein. While not wishing to be bound by theory,
protein aggregation is believed to be one of mechanisms by which
benefit agent of high polarity (defined by HSP of 16.5 to 37,
preferably 17 to 30) protects protein (e.g., from being "attached"
by surfactant(s))
[0016] FIG. 4 shows that, as amount of benefit agent is increased,
the amount of heat that is needed to denature protein used in
combination with the benefit agent is increased. Again, while not
wishing to be bound by theory, protection from denaturation is
believed to be another mechanism by which benefit agent protects
protein from attack by surfactant(s).
[0017] FIG. 5 shows that, without benefit agent of higher polarity
(defined by HSP), protein will be denatured by surfactant at much
lower temperature than if benefit agent is used.
[0018] FIG. 6 shows the correlation between the in-vitro surfactant
binding to protein and in-vivo skin irritation. As more molecules
are binded (e.g., because of HSP outside defined optimal window),
mean irritation increases.
DETAILED DESCRIPTION OF THE INVENTION
[0019] The present invention relates to the fundamental observation
that, when a surfactant system which normally causes damage to skin
or other substrate (e.g., by causing denaturing of protein) is used
in combination with benefit agent or agents of a defined polarity,
the surfactant damage (measured by the number of surfactant
molecular binding sites binded per protein molecule) caused by the
surfactant can be reduced.
[0020] In one embodiment of the invention, the invention relates to
a method of reducing surfactant damage (measurable, for example, by
reduction in number of surfactant binding per protein molecule) of
at least about 5% compared to number of sites binded using
surfactant(s) and no benefit agent or benefit agent outside
polarity window, wherein said method comprises, in compositions
comprising at least one surfactant and at least one benefit agent,
using a benefit agent or combination of benefit agents having high
polarity. Polarity of benefit agents so used can be expressed as a
function of the HSP. In another embodiment, the invention relates
to a method of selecting benefit agent(s) suitable for reducing the
surfactant damage.
Surfactant
[0021] Preferably, although not necessarily, the at least one
surfactant should be an anionic surfactant and, if a mixture of
surfactants is used, at least one of said mixture should be an
anionic surfactant.
[0022] Surfactant(s), when used in a fully formulated composition,
may comprise from 2% to 90% of the composition, depending on
whether the surfactants are formulated as part of a bar
composition, liquid composition, cream, etc.
[0023] For example, if part of a rinse-off liquid cleanser
composition, surfactant or surfactants may comprise 2 to 75% of a
surfactant selected from the group consisting of anionic, nonionic,
amphoteric/zwitterionic, cationic surfactant and mixtures
thereof.
[0024] Among suitable anionic actives which may be used are the
alkyl ether sulfates, acyl isethionates, alkyl ether sulfonates,
sarcosinates, sulfosuccinates, taurates and combinations thereof.
Among suitable amphoteric actives may be included alkylbetaines,
amidopropyl betaines, amidopropyl sultaines and combinations
thereof.
[0025] Alkyl ether sulfates of the present invention may be of the
general formula R--(OCH.sub.2CH.sub.2).sub.nOSO.sub.3-M.sup.+
[0026] wherein R ranges from C.sub.8-C.sub.20 alkyl, preferably
C.sub.12-C.sub.15 alkyl, n is an integer from 1 to 40, preferably
from 2 to 9, optimally about 3, and M.sup.+ is a sodium, potassium,
ammonium or triethanolammonium cation.
[0027] Typical commercial co-actives of this variety are listed in
the Table below: TABLE-US-00001 Physical Trademark Chemical Name
Form Manufacturer Steol CS 330 Sodium Laureth Liquid Stepan Sulfate
Standopol ES-3 Sodium Laureth Liquid Henkel Sulfate Alkasurf ES-60
Sodium Laureth Paste Alkaril Sulfate Cycloryl TD TEA Laureth Paste
Cyclo Sulfate Standopol 125-E Sodium Laureth- Liquid Henkel 12
Sulfate Cedepal TD407MF Sodium Trideceth Paste Miranol Sulfate
Standopol EA-2 Ammonium Laureth Liquid Henkel Sulfate
[0028] Alkyl ether sulfonates may also be employed for the present
invention. Illustrative of this category is a commercial product
known as Avenel S-150 commonly known as a sodium C.sub.12-C.sub.15
Pareth-15 sulfonate.
[0029] Another active type suitable for use in the present
invention is that of the sulfosuccinates. This category is best
represented by the monoalkyl sulfosuccinates having the formula
R.sub.2OCCH.sub.2CH(SO.sub.3XNa.sup.+)COOXM.sup.+; and amido-MEA
sulfosuccinates of the formula:
RCONHCH.sub.2CH.sub.2O.sub.2CCH.sub.2CH(SO.sub.3XM.sup.+)COOXM.sup.+;
wherein R ranges from C.sub.8-C.sub.20 alkyl, preferably
C.sub.12-C.sub.15 alkyl and M.sup.+ is a sodium, potassium,
ammonium or triethanolammonium cation. Typical commercial products
representative of these co-actives are those listed in the Table
below: TABLE-US-00002 Physical Trademark Chemical Name Form
Manufacturer Emcol 4400-1 Disodium Lauryl Solid Witco
Sulfosuccinate Witco C5690 Disodium Liquid Witco Cocoamido MEA
Sulfosuccinate McIntyre Disodium Liquid McIntyre Mackanate CM40F
Cocoamido MEA Sulfosuccinate Schercopol Disodium Liquid Scher CMSNa
Cocoamido MEA Sulfosuccinate Emcol 4100M Disodium Paste Witco
Myristamido MEA Sulfosuccinate Schercopol Disodium Liquid Scher
Oleamido MEA Varsulf S13333 Disodium Solid Scherex Ricionoleamido
MEA Sulfosuccinate
[0030] Sarcosinates may also be useful in the present invention as
a co-active. This category is indicated by the general formula
RCON(CH.sub.3)CH.sub.2CO.sub.2XM.sup.+, wherein R ranges from
C.sub.8-C.sub.20 alkyl, preferably C.sub.12-C.sub.15 alkyl and
M.sup.+ is a sodium, potassium ammonium or triethanolammonium
cation. Typical commercial products representative of these
co-actives are those listed in the Table below: TABLE-US-00003
Physical Trademark Chemical Name Form Manufacturer Hamposyl L-95
Sodium Lauroyl Solid W. R. Grace Sarcosinate Hamposyl TOC-30 TEA
Cocoyl/ Liquid W. R. Grace Sarcosinate
[0031] Taurates may also be employed in the present invention as
co-actives. These materials are generally identified by the formula
RCONR.sup.1CH.sub.2CH.sub.2SO.sub.3XM.sup.+ , wherein R ranges from
C.sub.8-C.sub.20 alkyl, preferably C.sub.12-C.sub.15 alkyl, R.sup.1
ranges from C.sub.1-C.sub.4 alkyl, and M.sup.+ is a sodium,
potassium, ammonium or triethanolammonium cation. Typical
commercial products representative of these co-actives are those
listed in the Table below: TABLE-US-00004 Physical Trademark
Chemical Name Form Manufacturer Igepon TC 42 Sodium Methyl Paste
GAF Cocoyl Taurate Igepon T-77 Sodium Methyl Paste GAF Oleoyl
Taurate
[0032] Within the category of amphoterics there are three general
categories suitable for the present invention. These include
alkylbetaines of the formula
RN.sup.+(CH.sub.3).sub.2CH.sub.2CO.sub.2XM.sup.+, amidopropyl
betaines of the formula
RCONHCH.sub.2CH.sub.2CH.sub.2N.sup.+(CH.sub.3).sub.2CH.sub.2CO.sub.2XM.su-
p.+, and amidopropyl sultaines of the formula
RCONHCH.sub.2CH.sub.2N.sup.+(CH.sub.3).sub.2CH.sub.2SO.sub.3XM.sup.+
wherein R ranges from C.sub.8-C.sub.20 alkyl, preferably
C.sub.12-C.sub.15 alkyl, and M.sup.+ is a sodium, potassium,
ammonium or triethanolammonium cation. Typical commercial products
representative of these co-actives are found in the Table below:
TABLE-US-00005 Physical Trademark Chemical Name Form Manufacturer
Tegobetaine F Cocamidopropyl Liquid Goldschmidt Betaine Lonzaine C
Cocamidopropyl Liquid Lonza Betaine Lonzaine CS Cocamidopropyl
Liquid Lonza Hydroxysultaine Lonzaine 12C Coco-Betaine Liquid Lonza
Schercotaine MAB Myristamidopropyl Liquid Lonza Betaine Velvetex
OLB-50 Oleyl Betaine Paste Henkel
[0033] Within the broad category of liquid actives, the most
effective are the alkyl sulfates, alkyl ether sulfates, alkyl ether
sulfonates, sulfosuccinates, and amidopropyl betaines.
[0034] Another preferred surfactant is an acyl isethionate having
the formula ##STR1## in which R denotes a linear or branched alkyl
group and M denotes an alkali metal or alkaline earth metal or an
amine.
[0035] Another surfactant which may be used are the monoalkyl or
dialkylphosphate surfactants.
[0036] Another surfactant which may be used, preferably used as
primary surfactant in combination with other surfactants noted
above, is sodium coco glyceryl ether sulfonate. While desirable to
use because of its mildness properties, this coco AGS alone does
not provide optimum lather creaminess. A sodium 90/10
coconut/tallow alkyl AGS distribution is preferred for creaminess.
Salts other than the sodium salt such as TEA-, ammonium, and K-AGS
and chain length distributions other than 90/10 coconut/tallow are
usable at moderate levels. Also, some soap may be added to improve
lather volume and speed of lathering. Certain secondary
co-surfactants used in combination with AGS can also provide a
creamier and more stable lather. These secondary surfactants should
also be intrinsically mild. One secondary surfactant that has been
found to be especially desirable is sodium lauroyl sarcosinate
(trade name Hamposyl L, made by Hampshire Chemical).
[0037] The amphoteric betaines and sultaines noted above can be
used as the sole surfactant, but are more preferred as a
co-surfactant. Nonionics generally should not be used as the sole
surfactant in this product if high foaming is desirable; however,
they can be incorporated as a co-surfactant.
[0038] Nonionic and cationic surfactants which may be used include
any one of those described in U.S. Pat. No. 3,761,418 to Parran,
Jr., hereby incorporated by reference into the subject application.
Also included are the aldobionamides as taught in U.S. Pat. No.
5,389,279 to Au et al; and the polyhydroxy fatty acid amides as
taught in U.S. Pat. No. 5,312,934 to Letton, both of which are
incorporated by reference into the subject application.
[0039] Soaps may also be used. The soaps may be added neat or made
in situ via adding a base, e.g., NaOH; to convert free fatty
acids.
[0040] A preferred surfactant active system is one such that acyl
isethionate comprises 1 to 15% by weight of the total composition
and/or an anionic other than acyl isethionate (e.g., ammonium
lauryl ether sulfate) comprises 1 to 15% by weight of the total
composition and amphoteric comprises 0.5 to 15% by weight of the
total composition.
[0041] Another preferred active system is one comprising 1 to 20%
alkyl ether sulfate. Preferred surfactant systems may also contain
1 to 10% alkali metal lauryl sulfate or C.sub.14-C.sub.16 olefin
sulphonate instead of acyl isethionate.
[0042] Also, in the preferred embodiment, the Hansen solubility
parameter of the benefit agent or benefits agents used in
combination with the surfactant system should be between 16.5 and
37, preferably 17 and 30, more preferably 19 and 27. The benefit
agent(s) generally comprise 0.1 to 50% by wt., preferably 0.5 to
30%, more preferably 1 to 25% by wt. of the final compositions.
[0043] Hansen solubility parameter is the total energy of
vaporization of a liquid. This total energies consists of several
individual parts arising from (atomic) dispersion forces,
(molecular) permanent dipole-permanent dipole forces, and
(molecular) hydrogen bonding (electron exchange). The basic
equation which governs the assignment of Hansen parameters is that
the total cohesion energy, E, must be the sum of the individual
energies which make it up. E=E.sub.D+E.sub.P+E.sub.H where E.sub.D,
E.sub.P, E.sub.H are the dispersion cohesion energy, polar cohesion
energy and hydrogen bonding cohesion energy, respectively. The
Hansen solubility parameter (.delta., in unit MPa.sup.1/2) is thus
defined as:
.delta.2=(E.sub.D/V)+(E.sub.P/V)+(E.sub.H/V)=.delta.2.sub.D+.delta.2.sub.-
P+.delta.2.sub.H where V is the molar volume, and .delta..sup.D,
.delta..sub.P, .delta..sub.H are the Hansen D (dispersion cohesion
energy), P (polar cohesion energy) and H (hydrogen bonding cohesion
energy).
[0044] As noted the benefit agent may be used in a fully formulated
composition in an amount from about 0.1 to 50% by wt., depending on
form of composition.
[0045] Examples of oil/solvent or oil/solvent systems having HSP
with ranges of invention include alkyl lactate (e.g.. butyl
lactate), alkyl alcohols (e.g., octyl dodeconol), alcohol such as
ethanol, butanol etc.
[0046] In a second embodiment of the invention, the invention
comprises a method of selecting oil(s)/solvent(s) to be used to
reduce surfactant damage in a composition comprising at least one
surfactant and benefit agent, wherein said process comprises:
[0047] (1) determining Hansen solubility parameter of a benefit
agent (e.g., by testing or by finding in literature; and/or by
using molecular modeling software); and [0048] (2) selecting said
benefit agent(s) having a Hansen solubility parameter of between
16.5 and 37, preferably 17 and 30, more preferably 19 to 27.
[0049] Reduction in surfactant damage may be defined by reduction
in number of binding sites binded by surfactant(s) to given protein
when surfactant(s) are used in combination with oil/solvent
compared to where surfactant alone is used.
[0050] Specifically the reduction may be defined in reduction of
sites binded of at least about 5%, preferably at least about 10%,
more preferably at least about 10% to 50% (and preferably higher)
relative to composition without benefit agent or relative to
composition with benefit agent outside the defined polarity
window.
[0051] In a third embodiment, the invention relates to compositions
comprising surfactant and a benefit agent or combination of benefit
agents having solubility parameter from 16.5 to 37; said
composition have reduced surfactant damage. Again, damage is
measured by reduction in sites on surfactant binded of at least 5%,
preferably at least 10% relative to composition with same
surfactant type and amount comprising benefit agent(s) with HSP
below 16.5 or above 37, or relative to composition with same type
and amount of surfactant and no benefit agent.
Definitions
[0052] SDS=Sodium dodecyl sulfate [0053] SLES=Sodium lauryl ether
sulfate [0054] CAPB=Cocoamidopropybetaine [0055] CETIOL
OE=Dicaprylyl ether [0056] IPM=Isopropylmyristate [0057] Castor oil
318 (also known as Surfactol.RTM. 318 from CasChem, Inc. in
Bayonne, N.J.) is ethoxylated castor oil with on average 5 PEG unit
per castor oil molecule [0058] Castor oil 365 (also known as
Surfactol.RTM. 365 from CasChem, Inc. in Bayonne, N.J.) is
ethoxylated castor oil with on average 40 PEG unit per castor oil
molecule [0059] BSA=Bovine serum albumin [0060] HPLC=High
performance liquid chromatography [0061] DSC=Differetial Scanning
chromatography [0062] B*=The Commission International de
l'Eclairage (CIE) L*a*b* color system is used an objective
measurement parameter for color. In the 3-dimensional space, L*
(luminescence) represents the grey level from black to white, a*
represents the green-red component and b* the blue-yellow
component. Methodology/Protocol Conductivity Test:
[0063] Conductance measurements were carried out at room
temperature by use of a Thermo conductivity meter, model Orion
150+. Routinely, the titrations were performed by adding a
controlled amount of 10% of stock surfactant solution under
magnetic stirring into the 0.5% BSA (Bovine Serum Albumin) in 0.02M
acetate buffer at pH.about.5.2. Values of CMC (critical
micellization concentration), CAC (critical aggregation
concentration) and protein saturation point (PSP) were defined by
the changing of the slope of the conductivity vs. surfactant
concentration plots. The number of surfactants binding to each
protein can be calculated by:
{[PSP]-[CAC]}/{[protein]/Mw.sub.protein}, where [protein] is the
protein concentration.
Indigo Carmine Surfactant/Dye Binding Procedure
[0064] A modification of the procedure described by Imokawa and
Mishima (Contact Dermatitis 5:357-366, 1979) was used. Two mls of
each surfactant sample were placed into plastic chambers resting on
the volar forearm skin (area .about.3.14 cm.sup.2) for 2 minutes.
The samples were removed, and the sites rinsed with 2 mls of
deionized water. Two mls of 1% Indigo carmine dye were then added
to each chamber for 1 minute and then the sites were rinsed with 2
mls of deionized water. The sites were patted dry with a paper
towel. Digital images were obtained for each arm, and each skin
site was measured for its L*a*b* values using a Minolta CM 508D.
The Commission International de l'Eclairage (CIE) L*a*b* color
system is used an objective measurement parameter for color. In the
3-dimensional space, L* (luminescence) represents the grey level
from black to white, a* represents the green-red component and b*
the blue-yellow component. In this study, each skin site was
measured for its L*a*b* values using a Minolta CM 508D
spectrophotometer.
[0065] The Minolta CM 508D takes three readings on each test site
and reports the average. Three sets of average readings were
obtained for each site and the values averaged again.
HPLC Test For Surfactant Deposition:
[0066] 8 weeks old white pig skin was shaved and washed in warm
water. Ethanol sprayed and rinse/wiped with wipeall, and then
stored it at -7.degree. C. Dose controlled amount of surfactant
sample (3.3 mg of per cm.sup.2) onto pig skin of known surfactant
area. Rub for 30 sec. Let stand for 1.5 min. And then rinse for 10
sec under 100.degree. F. running water. Pat dry and let the skin
dry in the hood for around 10 min. Then perform 3 times 1 min
extraction using 2 ml mixture solvent (25% chloroform/25% water/50%
methanol, by volume) on pig skin for surfactant extraction.
Evaporate solvent under liquid N.sub.2 and dissolve the content in
the vial with 0.5 ml of mobile phase for HPLC analysis using ELSD
2000 detector.
Dynamic Light Scattering For Protein Size:
[0067] The size of protein molecule was measured by 90Plus/Bi-MAS
multi angle particle size, BrokeHaven. The scattering angle is
90.degree. and the wavelength is 635 nm. 0.5% of protein in acetate
buffer (pH=5.2, IS=0.02M) was used. The protein sample was filtered
three times by a syringe filter with 0.1 .mu.m pore size Nylon
membrane prior to the measurement. All experiments were carried out
at room temperature (25.degree. C.). The scattered field
autocorrelation function (g(q, .tau.)) vs. delay time (.tau.) was
obtained from each measurement. A cumulant model was used to fit
the autocorrelation function with the delay time to calculate the
size of the protein.
Micro--DSC For Protein Denaturation:
[0068] 1.2% of BSA acetate buffer solution was prepared (pH 5.2, IS
0.02). An accurately measured amount of sample solution was loaded
in DSC sample chamber and the thermal behavior of the sample was
studied over the range of 5 to 102.degree. C. at a heating rate of
0.5.degree. C./min. Then the BSA acetate solution was titrated with
either oil, or surfactant, or oil/surfactant at 1:1 ratio. After
each titration, a DSC measurement was performed.
14-Day Cumulative In Vivo Patch Test
[0069] A randomized, double-blind study was conducted and consisted
of one cell, with 24 subjects 18-65 years of age. Patching occurred
for 14 consecutive days, except on Sundays. Patches applied on
Saturday were left in place until Monday, when freshly prepared
patches were applied. The designated patch test sites were
approximately 2 cm.times.2 cm on the intrascapular area of the
back, and approximately 0.2 ml of test product was applied to each
patch. Each day following application, the patches were removed,
the sites evaluated for irritation, and identical patches reapplied
to the same test sites. Monday's irritation scores also were
recorded as Sunday's scores, with Sundays being counted as exposure
days. Individual test article scores were calculated via summation
of the results for each day. Cumulative irritation scores were the
sum of the numerical irritation grades assigned daily during the
14-day test period.
EXAMPLE 1-10 & COMPARATIVES A & B
[0070] In order to show the effect of benefit agent having
different polarity on binding to protein molecule (a reflection of
the harshness of surfactant; more surfactant binding to protein
equal harsher and more damage expected), applicants tested
surfactant binding of (1) surfactant alone and (2) of surfactant in
combination with various oils/cosolvents (at 1:1 surfactant to oil
ratio) to see level of (how many) surfactants binding per protein
molecule (e.g., BSA) at saturation. The tests were done using
conductivity test described in protocol and results are set forth
below in Table 1. TABLE-US-00006 TABLE 1 Surfactant binding to BSA
protein measured by conductivity: 10% SDS with 10% oil compared to
10% SDS alone. Saturated Hansen binding: solubility No. of
parameter of surfactant oil/cosolvent per BSA at Example
(MPa.sup.1/2) saturation 10% SDS (surfactant alone) Control -- 220
10% SDS + 10% butyl 1 19.58 169 lactate 10% SDS + 10% octyl 2 16.98
189 dodecanol 10% SDS + 10% wickenol 3 18.56 192 10% SDS + 10%
cetiol OE 4 16.85 201 10% SDS + 10% IPM A 16.02 237 10% SDS + 10%
dodecane B 16.02 243 10% SDS + 10% triolein 5 23.77 172 10% SDS +
10% glycerin 6 36.46 202 10% SDS + 10% methanol 7 29.64 188 10% SDS
+ 10% ethanol 8 26.49 158 10% SDS + 10% butanol 9 23.28 141 10% SDS
+ 10% hexanol 10 21.11 99
[0071] As seen, in most cases the number of surfactants binded by
BSA went down when oil solvent was added (since surfactant binding
is associated with harshness, this is desirable).
[0072] On a molecular level, it can be noted that different
oils/water soluble solvents have different effect on surfactant
binding to protein. Thus, as seen from comparatives A & B
(where the Hansen solubility of oil and/or cosolvent was about 16)
there was little reduction in number of surfactants binding
compared to control with no oil/cosolvent); with other
oils/cosolvent there was a mild level of reduction; and with yet
other oil/cosolvents (see Example 1 or 5) reduction was quite
significant.
[0073] Applicants believe there is an optimized polarity window
(defined by Hansen solubility parameter of about 16.5 to 37,
preferably 17 to 30, more preferably 19 to 27 where most
significant reduction is found.
[0074] On a macro level, Examples 17-18 and 19 below show that,
where polar oil/solvent reduce surfactant binding as measured on a
molecular level, surfactant deposition onto skin after wash is also
reduced. Therefore, there is a clear link between surfactant
binding to protein molecule and surfactant binding to skin during
wash.
[0075] Further, in a patch test (see Example 23 and FIG. 6), there
is a strong correlation between the irritation score and the
surfactant binding to protein in molecular level.
EXAMPLES 11-16
[0076] Applicants conducted same test as in Examples 1 to 10, but
used SLES/CAPB surfactant system instead of SDS. Results are set
forth in Table 2 TABLE-US-00007 TABLE 2 Surfactant binding to BSA
protein measured by conductivity: 10% SLES/CAPB (2:1) with 10% oil
compared to 10% SLES/CAPB (2:1) alone Saturated Hansen binding:
solubility No. of parameter of surfactant oil/cosolvent, per BSA at
Example (MPa.sup.1/2) saturation 10% SLES/CAPB (2:1) Control -- 183
10% SLES/CAPB (2:1) + 11 19.58 95 10% butyl lactate 10% SLES/CAPB
(2:1) + 12 16.98 97 10% octyl dodecanol 10% SLES/CAPB (2:1) + 13
18.56 145 10% wickenol 10% SLES/CAPB (2:1) + 14 16.85 160 10%
cetiol DE 10% SLES/CAPB (2:1) + C 16.02 165 10% IPM 10% SLES/CAPB
(2:1) + D 16.02 192 10% dodecane 10% SLES/CAPB (2:1) + 15 23.77 110
10% triolein 10% SLES/CAPB (2:1) + 16 36.46 150 10% glycerin
[0077] This example, similar to Examples 1-10, is showing that the
effect of benefit agent(s) to reduce surfactant binding to protein
is dependent on the polarity of the benefit agent: the higher the
polarity, the more effective to reduce surfactant binding to
protein. There is a window of solubility parameter (from 16.5 to
37, or preferably from 17 to 30, more preferably 19 to 27) that
offers the most reduction on surfactant binding to protein.
[0078] Importantly, it should be noted is that the choice of
oil/solvent to most efficiently reduce surfactant binding to
protein is not dependent on surfactant type.
EXAMPLES 17-18
[0079] In order to further show the protective effect of benefit
agent (e.g., oil), applicants compared surfactant deposition onto
skin after wash, using solvent extraction and HPLC method defined
in protocol section, for 10% SDS alone and compared with 10% SDS
used with dodecane; or used with triolein. Results are seen in FIG.
1 and the amount of SDS deposition on skin after wash is also
listed in Table 3 below: TABLE-US-00008 TABLE 3 Surfactant
Deposition Onto Pig Skin after Wash Examined by Solvent Extraction
After Skin Wash and HPIC SDS deposition on Example skin
(.mu.g/cm.sup.2) 10% SDS Control 17.6 10% SDS + 10% dodecane 17
15.9 10% SDS + 10% triolein 18 11.9
[0080] From FIG. 1 and Table 3, it was found that pig skin washed
with SDS has the highest amount of SDS surfactant deposited
(17.6+/-1.2 .mu.g/cm2); that pig skin washed with SDS+dodecane (1:1
surfactant to oil ratio) has slightly lower SDS surfactant
deposition (15.9+/-0.5 .mu.g/cm.sup.2); while pig skin washed with
SDS +/- triolein (1:1 surfactant to oil ratio) has significantly
lower SDS surfactant deposition (11.9 +/-0.5 .mu.g/cm.sup.2). Note
that from the in-vitro surfactant binding to protein molecule data
shown in Example 1, polar oil such as triolein leads to less
surfactant binding to protein on the molecular level than non-polar
oil such as dodecane. Therefore, the in-vivo surfactant deposition
data and the in-vitro surfactant-protein binding data agree with
each other, indicating that polar oil such as triolein will lead to
less surfactant binding both on the micro-scale level (surfactant
molecule binds to protein molecule) and on the macro-scale level
(surfactant binds to skin during wash).
EXAMPLE 19
[0081] Applicants again ran a test using SDS versus SDS and
dodecane versus SDS and triolein and results are set forth in FIG.
2. Here test measured binding to human forearm during washing
(indigo carmine staining test to skin) and 0.5% of each of the
three solutions was used to test. A lower b* value indicates less
surfactant binding on skin. As shown in FIG. 2, forearm washing
with SDS+triolein (a polar oil) shows a lower b* value than SDS
alone and SDS+dodecane (a non-polar oil), indicating less
surfactant binding to skin after awash. This example once again
shows that polar benefit agent (e.g., oil) reduces surfactant
binding better than non-polar benefit agent.
EXAMPLE 20
[0082] While not wishing to be bound by theory, applicants believe
that one mechanism by which benefit agent protects surfactant from
denaturation (and exposure to surfactant) is by inducing protein
aggregation.
[0083] In this regard, applicants measured size of protein (using
sunflower seed oil and BSA protein) by dynamic light scattering
technique described in protocol section to determine extent of oil
induced protein aggregation. As seen from FIG. 3, at roughly 1 to 5
ratio of benefit agent to protein, an in protein size was detected
by dynamic light scattering thereby indicating aggregation of
protein.
EXAMPLE 21
[0084] Again, while not wishing to be bound by theory, applicants
believe benefit agent (e.g., oil) helps stabilize protein from
denaturation (and greater exposure to surfactant) by increasing the
heat needed to denature the protein.
[0085] In this regard, using DSC measurement technique described in
methodology section applicants determined that protein alone (BSA)
has denaturation enthalpy of about 497 KJ/mol. As indicted in FIG.
4, addition of triolein to the protein solution increases heat
needed to achieve denaturation until it reaches a plateau at
oil/protein ratio of 1 to 5.
EXAMPLE 22
[0086] Again, using DSC data (as shown in FIG. 5), applicants
determined that, without benefit agent, SDS willfully denature BSA
protein when at room temperature (indicated by denaturation
enthalpy approaching zero) at a ratio of about 1.2 to 1 surfactant
to protein. However, when there is a 1:1 mixture of SDS triolein,
BSA protein is not fully denatured at room temperature until about
ratio of 1.8 surfactant to protein. This data clearly indicates
that triolein is protecting BSA from surfactant damage.
EXAMPLE 23
[0087] In FIG. 6, the in-vitro surfactant binding to protein data
was compared to in vivo skin irritation data (measured according to
the "14-Day Cumulative In vivo Patch Test" listed in protocol). As
shown in FIG. 6, the in vivo data positively correlated with the in
vitro findings (r.sup.2=0.887) that those polar oils (having higher
levels of alkoxylated) lead to less surfactant binding to protein
in-vivo also lead to less irritation in-vivo.
* * * * *